tbuckley/cabot-search huggingface dataset:
Novel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia
Authors: Waled Bahaj, Tariq Kewan, Carmelo Gurnari, Arda Durmaz, Ben Ponvilawan, Ishani Pandit, Yasuo Kubota, Olisaemeka D. Ogbue, Misam Zawit, Yazan Madanat, Taha Bat, Suresh K. Balasubramanian, Hussein Awada, Ramsha Ahmed, Minako Mori, Manja Meggendorfer, Torsten Haferlach, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Journal of Hematology & Oncology (2023)

Abstract Background TP53 mutations ( TP53 MT ) occur in diverse genomic configurations. Particularly, biallelic inactivation is associated with poor overall survival in cancer. Lesions affecting only one allele might not be directly leukemogenic, questioning the presence of cryptic biallelic subclones in cases with dismal prognosis. Methods We have collected clinical and molecular data of 7400 patients with myeloid neoplasms and applied a novel model by identifying an optimal VAF cutoff using a statistically robust strategy of sampling-based regression on survival data to accurately classify the TP53 allelic configuration and assess prognosis more precisely. Results Overall, TP53 MT were found in 1010 patients. Following the traditional criteria, 36% of the cases were classified as single hits, while 64% exhibited double hits genomic configuration. Using a newly developed molecular algorithm, we found that 579 (57%) patients had unequivocally biallelic, 239 (24%) likely contained biallelic, and 192 (19%) had most likely monoallelic TP53 MT . Interestingly, our method was able to upstage 192 out of 352 (54.5%) traditionally single hit lesions into a probable biallelic category. Such classification was further substantiated by a survival-based model built after re-categorization. Among cases traditionally considered monoallelic, the overall survival of those with probable monoallelic mutations was similar to the one of wild-type patients and was better than that of patients with a biallelic configuration. As a result, patients with certain biallelic hits, regardless of the disease subtype (AML or MDS), had a similar prognosis. Similar results were observed when the model was applied to an external cohort. In addition, single-cell DNA studies unveiled the biallelic nature of previously considered monoallelic cases. Conclusion Our novel approach more accurately resolves TP53 genomic configuration and uncovers genetic mosaicism for the use in the clinical setting to improve prognostic evaluation.
Sustainable Sources of Raw Materials for Additive Manufacturing of Bone‐Substituting Biomaterials
Authors: Niko E. Putra, Jie Zhou, Amir A. Zadpoor
Journal: Advanced Healthcare Materials (2023)

The need for sustainable development has never been more urgent, as the world continues to struggle with environmental challenges, such as climate change, pollution, and dwindling natural resources. The use of renewable and recycled waste materials as a source of raw materials for biomaterials and tissue engineering is a promising avenue for sustainable development. Although tissue engineering has rapidly developed, the challenges associated with fulfilling the increasing demand for bone substitutes and implants remain unresolved, particularly as the global population ages. This review provides an overview of waste materials, such as eggshells, seashells, fish residues, and agricultural biomass, that can be transformed into biomaterials for bone tissue engineering. While the development of recycled metals is in its early stages, the use of probiotics and renewable polymers to improve the biofunctionalities of bone implants is highlighted. Despite the advances of additive manufacturing (AM), studies on AM waste-derived bone-substitutes are limited. It is foreseeable that AM technologies can provide a more sustainable alternative to manufacturing biomaterials and implants. The preliminary results of eggshell and seashell-derived calcium phosphate and rice husk ash-derived silica can likely pave the way for more advanced applications of AM waste-derived biomaterials for sustainably addressing several unmet clinical applications.
Ann Robinson’s research reviews—3 August 2023
Authors: Ann Robinson
Journal: BMJ (2023)

S'not what it seemsCan you tell which snotty-nosed children have acute sinusitis rather than a cold or hayfever?If you diagnose acute sinusitis, do you prescribe antibiotics?And is the colour of their snot a factor in your decision?This useful US primary care study of 515 children aged 2-11 years diagnosed with acute sinusitis based on clinical criteria found a large overlap in symptoms with viral upper respiratory tract infections (no surprise there).Researchers found that 28% of children didn't grow any pathogenic bacteria from their nasopharynx.The children given antibiotics (amoxicillin and clavulanate for 10 days) had milder illness (mean symptom scores 9 v 10.6) and got better quicker (seven v nine days) than those given placebo.However, antibiotics had only minimal benefit in the 28% of children who didn't have any bacterial colonisation of their nasopharynx.And kids with yellow or green snot were no more likely to respond than those with the clear sort.Predictably, there was more diarrhoea in the antibiotic group (11.4% v 4.7%) but no serious adverse events in either group.My take home is that we should probably swab and wait for the results before randomly treating.
Cluster of Carbapenemase-Producing Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Among Patients in an Adult Intensive Care Unit — Idaho, 2021–2022
Authors: Megan E. Cahill, Martha Jaworski, Victoria Harcy, Erin Young, D. Cal Ham, Paige Gable, Kris K. Carter
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Treatment of carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) infections is challenging because of antibiotic resistance. CP-CRPA infections are highly transmissible in health care settings because they can spread from person to person and from environmental sources such as sink drains and toilets. During September 2021-January 2022, an Idaho hospital (hospital A) isolated CP-CRPA from sputum of two patients who stayed in the same intensive care unit (ICU) room (room X), 4 months apart. Both isolates had active-on-imipenem metallo-beta-lactamase (IMP) carbapenemase gene type 84 (blaIMP-84) and were characterized as multilocus sequence type 235 (ST235). A health care-associated infections team from the Idaho Division of Public Health visited hospital A during March 21-22, 2022, to discuss the cluster investigation with hospital A staff members and to collect environmental samples. CP-CRPA ST235 with blaIMP-84 was isolated from swab samples of one sink in room X, suggesting it was the likely environmental source of transmission. Recommended prevention and control measures included application of drain biofilm disinfectant, screening of future patients who stay in room X (e.g., the next 10 occupants) upon reopening, and continuing submission of carbapenem-resistant P. aeruginosa (CRPA) isolates to public health laboratories. Repeat environmental sampling did not detect any CRPA. As of December 2022, no additional CP-CRPA isolates had been reported by hospital A. Collaboration between health care facilities and public health agencies, including testing of CRPA isolates for carbapenemase genes and implementation of sink hygiene interventions, was critical in the identification of and response to this CP-CRPA cluster in a health care setting.
Protein-level mutant p53 reporters identify druggable rare precancerous clones in noncancerous tissues
Authors: Pengle Yao, Peng Xiao, Zongyao Huang, Min Tang, Xiwen Tang, Gaoxia Yang, Qi Zhang, Xinpei Li, Zhengnan Yang, Chuanxing Xie, Hui Gong, Guihua Wang, Yutong Liu, Xiuxuan Wang, Huifang Li, Da Jia, Lunzhi Dai, Lu Chen, Chong Chen, Yu Liu, Hengyi Xiao, Yan Zhang, Yuan Wang
Journal: Nature Cancer (2023)
Hallmarks of CD8+ T cell dysfunction are established within hours of tumor antigen encounter before cell division
Authors: Michael W. Rudloff, Paul Zumbo, Natalie R. Favret, Jessica J. Roetman, Carlos R. Detrés Román, Megan M. Erwin, Kristen A. Murray, Sriya T. Jonnakuti, Friederike Dündar, Doron Betel, Mary Philip
Journal: Nature Immunology (2023)
Soft and stretchable organic bioelectronics for continuous intraoperative neurophysiological monitoring during microsurgery
Authors: Wenjianlong Zhou, Yuanwen Jiang, Qin Xu, Liangpeng Chen, Hui Qiao, Yi-Xuan Wang, Jian-Cheng Lai, Donglai Zhong, Yuan Zhang, Weining Li, Yanru Du, Xuecheng Wang, Jiaxin Lei, Gehong Dong, Xiudong Guan, Shunchang Ma, Peng Kang, Linhao Yuan, Milin Zhang, Jeffrey B-H Tok, Deling Li, Zhenan Bao, Wang Jia
Journal: Nature Biomedical Engineering (2023)
Response to a letter to the editor on Darwin’s gemmules and extracellular vesicles: A striking resemblance
Authors: Owen G. Davies
Journal: Molecular Therapy (2023)

I would like to thank the authors of this letter for providing an interesting perspective and for publishing many thought-provoking articles on the topic of Darwin's pangenesis over the years. Darwin's gemmules and extracellular vesicles: A striking resemblanceHe et al.Molecular TherapyAugust 3, 2023In BriefWe read with great interest the recent review article pertaining to extracellular vesicles (EVs) by Davies.1 This review article is highly appreciated and summarizes a large body of experimental data and many new study results. It is of great interest and importance in regenerative medicine. However, this review article contains a minor point that needs a rethink. In the brief historical context, Davies correctly states that Charles Darwin pioneered the study of molecular transfer from cell to cell. Full-Text PDF
<i>Notes from the Field:</i> Measles Outbreak — Central Ohio, 2022–2023
Authors: Elizabeth C. Tiller, Nina B. Masters, Kelley L. Raines, Adria D. Mathis, Stephen N. Crooke, Rebecca C. Zwickl, Gavin K. French, Emily R. Alexy, Elizabeth M. Koch, Naomi E. Tucker, Elizabeth M. Wilson, Tiffany S. Krauss, Erica Leasure, Jeremy Budd, Laurie M. Billing, Courtney Dewart, Kara Tarter, Kristen Dickerson, Radhika Iyer, Alexandria N. Jones, Katia C. Halabi, Matthew C. Washam, David E. Sugerman, Mysheika W. Roberts
Journal: MMWR Morbidity and Mortality Weekly Report (2023)
<i>Notes from the Field: </i>Safety Monitoring of Novavax COVID-19 Vaccine Among Persons Aged ≥12 Years — United States, July 13, 2022–March 13, 2023
Authors: Brittney Romanson, Pedro L. Moro, John R. Su, Paige Marquez, Narayan Nair, Brendan Day, Allison DeSantis, Tom T. Shimabukuro
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

The NVX-CoV2373 (Novavax) COVID-19 vaccine is a recombinant spike protein nanoparticle vaccine with Matrix-M adjuvant.Novavax is authorized and recommended as a primary 2-dose monovalent vaccination series in persons aged ≥12 years to prevent COVID-19 and as a monovalent booster dose in persons aged ≥18 years who are unable to or unwilling to receive an mRNA COVID-19 bivalent vaccine (1).* VAERS reports are classified as serious if any of the following are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death.https:// www.accessdata.fda.
Optimizing the use of systemic corticosteroids in severe asthma (ROSA II project): a national Delphi consensus study
Authors: J. Marques, F. Duarte-Ramos, M.B. Ferreira, R. Lima, C. Lopes, A. Sokolova, F.S. Tonin, C.C. Loureiro
Journal: Pulmonology (2023)
Aberrant expression of interleukin-17A in mast cells contributes to the pathogenesis of hidradenitis suppurativa
Authors: Chia-Bao Chu, Chao-Chun Yang, Yuan-Yu Hsueh, Po-Chuan Chen, Yi-Kai Hong, Yu-Yun Kuo, Shaw-Jenq Tsai
Journal: British Journal of Dermatology (2023)

Hidradenitis suppurativa (HS) significantly diminishes the quality of life for patients. Delayed diagnosis represents a significant challenge in effectively managing HS.
Postzygotic gain-of-function variants in <i>FGFR2</i> in two patients with hair follicle naevus
Authors: Qing Cheng, Fang Yang, Ruzeng Xue, Huijun Wang, Zhimiao Lin
Journal: British Journal of Dermatology (2023)

Hair follicle naevus (HFN) is a rare benign hamartoma that predominantly affects the face and neck. The genetic basis of HFN remains unclear. We report on two cases of HFN caused by pathozygotic gain-of-function variants in FGFR2.
3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration
Authors: Hao Huang, Lei Qiang, Minjie Fan, Yihao Liu, Anchun Yang, Dongbiao Chang, Jinsheng Li, Tong Sun, Yiwei Wang, Ruoyi Guo, Hanjie Zhuang, Xiangyu Li, Tailin Guo, Jinwu Wang, Huan Tan, Pengfei Zheng, Jie Weng
Journal: Bioactive Materials (2023)

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32−, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32− and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.
National UK guidelines for the management of paediatric craniopharyngioma
Authors: Hoong-Wei Gan, Paul Morillon, Assunta Albanese, Kristian Aquilina, Chris Chandler, Yen-Ching Chang, Evangelos Drimtzias, Sarah Farndon, Thomas S Jacques, Márta Korbonits, Adam Kuczynski, Jennifer Limond, Louise Robinson, Ian Simmons, Nick Thomas, Sophie Thomas, Nicola Thorp, Faraneh Vargha-Khadem, Daniel Warren, Bassel Zebian, Conor Mallucci, Helen Alexandra Spoudeas
Journal: The Lancet Diabetes & Endocrinology (2023)
Space and Bond Synergistic Conjugation Controlling Multiple‐Aniline NIR‐II Absorption for Photoacoustic Imaging Guided Photothermal Therapy
Authors: Longcai Liu, Yi Pan, Luyi Ye, Tian Zhang, Yang Chen, Chen Liang, Dapeng Chen, Xiaozhou Mou, Xiaochen Dong, Yu Cai
Journal: Advanced Healthcare Materials (2023)

Abstract Currently, clinical photothermal therapy (PTT) is greatly limited by the poor tissue penetration of the excitation light sources in visible (390–780 nm) and first near‐infrared (NIR‐I, 780–900 nm) window. Herein, based on space and bond synergistic conjugation, a multiple‐aniline organic small molecule (TPD), is synthesized for high‐efficiency second near‐infrared (NIR‐II, 900–1700 nm) photoacoustic imaging guided PTT. With the heterogeneity of six nitrogen atoms in TPD, the lone electrons on the nitrogen atom and the π bond orbital on the benzene ring form multielectron conjugations with highly delocalized state, which endowed TPD with strong NIR‐II absorption (maximum peak at 925 nm). Besides, according to the single molecular reorganization, the alkyl side chains on TPD make more free space for intramolecular motion to enhance the photothermal conversion ability. Forming TPD nanoparticles (NPs) in J‐aggregation, they show a further bathochromic‐shifted absorbance (maximum peak at 976 nm) as well as a high photothermal conversion efficiency (66.7%) under NIR‐II laser irradiation. In vitro and in vivo experiments demonstrate that TPD NPs can effectively inhibit the growth of tumors without palpable side effects. The study provides a novel NIR‐II multiple‐aniline structure based on multielectron hyperconjugation, and opens a new design thought for photothermal agents.
Controversies regarding albumin therapy in cirrhosis
Authors: Jonel Trebicka, Guadalupe Garcia-Tsao
Journal: Hepatology (2023)

Albumin is the most abundant protein in the human body and is synthetized exclusively by the liver. Therefore, serum albumin levels are reduced in acute and/or chronic liver disease. In cirrhosis, low levels of albumin predict the outcome. In advanced cirrhosis, the quality of albumin is decreased due to high oxidative stress and a proinflammatory state. Therefore, the administration of i.v. albumin would seem to be of pathophysiological relevance and benefit. Yet, the questions that remain are who, when, how much, and how often. While albumin infusion is recommended after large-volume paracentesis, at diagnosis of spontaneous bacterial peritonitis, in acute kidney injury, and in hepatorenal syndrome, the amount and schedule of albumin to be administered require refinement, particularly given complications related to volume overload that have become increasingly apparent. Other indications for albumin such as infections other than spontaneous bacterial peritonitis, hyponatremia, HE, prevention of poor outcomes in hospitalized, and in outpatients with cirrhosis are still debated. The results of studies in these settings are either negative, controversial, or inconclusive. This sheds some doubts regarding the use of albumin as a "one size fits all" strategy. The indication and patient selection are crucial and not always intuitive. The amount and frequency also seem to play a role in the success or failure of albumin. This review will critically discuss the evidence and underline areas where there are indications for albumin use and others where evidence is still insufficient and will have to await the development/results of randomized controlled trials.
A Biomimetic Nanoplatform with Improved Inflammatory Targeting Behavior for ROS Scavenging‐Based Treatment of Ulcerative Colitis
Authors: Xiaofen Wang, Menglu Jiao, Fangzhen Tian, Xuan Lu, Huihuang Xiong, Fan Liu, Yiqun Wan, Xiaodong Zhang, Hao Wan
Journal: Advanced Healthcare Materials (2023)

Ulcerative colitis (UC), a refractory disease, has become a global problem. Herein, a biomimetic nanoplatform (AU-LIP-CM) comprising Au cluster enzymes (AU)-loaded liposomes (AU-LIP) camouflaged with the fusion membrane (CM) consisting of neutrophil (NC) and red blood cell (RBC) membrane is designed for the treatment of UC. Briefly, revealed by second near-infrared (NIR-II) imaging through collection of fluorescence emitting >1200 nm from AU, the improved inflammatory targeting behavior contributed by CM cloaking, which inherits abilities of inflammatory targeting and immune escape from NC and RBC, respectively, promotes specific accumulation of AU within inflammatory intestines with up to ≈11.5 times higher than that of bare AU. Afterward, AU possessing superoxide dismutase- and catalase-like activities realizes high-efficiency scavenging of reactive oxygen species (ROS), leading to repair of intestinal barriers, regulation of the immune system, and modulation of gut microbiota, which surpass first-line UC drug. In addition, study of underlying therapeutic mechanism demonstrated that the treatment with AU-LIP-CM can alter the gene signature associated with response to ROS for UC mice to a profile similar to that of healthy mice, deciphering related signal pathways. The strategy developed here provides insights of learning from properties of natural bio-substances to empower biomimetic nanoplatform to confront diseases.
Invasive beta-haemolytic streptococcal infections, Finland, 2006 to 2020: increase in Lancefield group C/G infections
Authors: Dafni Katerina Paspaliari, Emmi Sarvikivi, Jukka Ollgren, Jaana Vuopio
Journal: Eurosurveillance (2023)

Background Invasive infections with beta-haemolytic streptococci of Lancefield groups A (iGAS), B (iGBS) and C/G (iGCGS) are a major cause of morbidity and mortality worldwide. Aim We studied incidence trends of invasive beta-haemolytic streptococcal infections in Finland, focusing on iGCGS. Methods We conducted a retrospective register-based study. Cases were defined as isolations from blood and/or cerebrospinal fluid and retrieved from the National Infectious Disease Register where all invasive cases are mandatorily notified. Results Between 2006 and 2020, the mean annual incidence was 4.1 per 100,000 for iGAS (range: 2.1–6.7), 5.2 for iGBS (4.0–6.3) and 10.1 for iGCGS (5.4–17.6). The incidence displayed an increasing trend for all groups, albeit for iGBS only for individuals 45 years and older. The increase was particularly sharp for iGCGS (8% annual relative increase). The incidence rate was higher in males for iGCGS (adjusted incidence rate ratio (IRR) = 1.6; 95% confidence interval (CI): 1.5–1.8) and iGAS (adjusted IRR = 1.3; 95% CI: 1.1–1.4); for iGBS, the association with sex was age-dependent. In adults, iGCGS incidence increased significantly with age. Recurrency was seen for iGCGS and secondarily iGBS, but not for iGAS. Infections with iGCGS and iGBS peaked in July and August. Conclusions The incidence of invasive beta-haemolytic streptococcal infections in Finland has been rising since 2006, especially for iGCGS and among the elderly population. However, national surveillance still focuses on iGAS and iGBS, and European Union-wide surveillance is lacking. We recommend that surveillance of iGCGS be enhanced, including systematic collection and typing of isolates, to guide infection prevention strategies.
Meet the First Authors
Authors: Paul Régnier
Journal: Circulation Research (2023)

is originally from France, and first earned a License in Life and Health Sciences, then an MS in Immunology from Université Paris Cité.Afterwards, he earned a PhD for his work on the complex link between cancer, dendritic cells and immune responses (INSERM U1151, Immunoregulation and Immunopathology team).He then joined the Immunology-Immunopathology-Immunotherapy (i3) laboratory (INSERM UMRS-959) and focused on the study of several human autoimmune/ autoinflammatory diseases, especially vasculitis.Complementarily, Paul also mastered R language programming and bioinformatics, and developed tools allowing him to automatize the analysis of different biological data types like flow cytometry, immunofluorescence and transcriptomics. Loss of Zfhx3 Results in Atrial Arrhythmias (p 313)Dr Heather Jameson earned her PhD from George Washington University studying the stress-induced elevations in heart rate and blood pressure that occur in obstructive sleep apnea.